ИСТИНА

Caloric restriction (CR) has positive effects on brain function and lifespan. A role of astrocytes in these effects is still unknown. We performed the study of changes in astrocytes in 4 months old mice after one month of calorically restricted diet consisting in 70% calories of ad libitum fed group. CR mice presented a small weight loss, while the control group receiving food ad libitum showed a small weight gain. No significant changes in the astrocyte density were observed in stratum radiatum of hippocampal CA1 in both groups. Astrocytes were recorded in whole-cell voltage-clamp mode for electrophysiological analysis and simultaneously loaded with Alexa Fluor 594 for two-photon microscopy morphological study. CR did not produce significant remodeling in astrocytic branches resolved with the diffraction limited microscopy. However, estimated volume fraction of unresolved presynaptic leaflets was significantly increased after CR. The number of cells coupled through the gap-junctions in the astrocytic syncytium was however significantly reduced after CR, but no difference in the length constant of coupling was detected. Morphological remodeling was accompanied by activity-dependent facilitation of synaptically-induced K + current and faster K + clearance in CR astrocytes. The activity-dependent facilitation of glutamate transporter current was not different in CR and control mouse astrocytes. However, activity-dependent prolongation of transporter current was abolished in CR. These findings suggest that reduced glutamate spillover and increased K + clearance occur due to enhanced astrocytic coverage of synapses in CR mice. Next, we performed confocal Ca 2+ imaging in astrocytes stained with Oregon Green BAPTA-AM in CA1 stratum radiatum of hippocampal slices. Spontaneous Ca 2+ event size decreased in astrocytic network after CR. However, the event duration was increased. Hence, not significant difference was observed in the Ca 2+ event integral. The long-term potentiation was significantly enhanced in CA1 after CR. We suggest that CR increases astrocytic coverage of synapses and promotes synaptic plasticity. These results may explain the effects of CR on the brain function.